Introduction: Dermal drug delivery to treat skin infections uses drugs topically, and is superior to oral drug delivery. This delivery method reduces systemic absorption and reduces the hepatic metabolism of the drugs. It also has a fixed and controlled drug input source that can prevent the changes of drug levels in the plasma. The most crucial barrier to dermal delivery is the stratum corneum, which acts as a barrier to drug penetration. Topical use of conventional drug formulations causes side effects and a lack of targeted drug delivery. Therefore, nanocarriers are used for topical drug delivery to overcome the obstacles to the targeted dermal layer. One of the nanocarriers is niosomes. In this study, a niosomal formulation containing doxycycline, the safest and most influential of tetracycline antibiotics, with a molar ratio of 8: 2 span 60/cholesterol was prepared and characterized
Methods: Niosomal formulation preparation method
The thin-film hydration method was used for niosomal formulation. First, the appropriate values of span60 and cholesterol with an 8:2 molar ratio and the total lipid of 700μmol were dissolved in 15 ml of chloroform and then transferred to a rotary evaporator at 60°C and 120rpm under reduced pressure. After chloroform evaporation, the thin film inside the balloon was hydrated by the drug solution at at 80rpm and 60°C (10μmol of doxycycline in 15ml PBS (pH=7.4)) under normal pressure for 60 minutes.
Size reduction methods
Three methods were used:
Bath sonicator: 5ml of suspension was sonicated for 45 minutes.
Extrusion: 5ml of suspension was passed five times through a polycarbonate membrane with a porosity size of 200nm.
Probe sonicator: 5ml of suspension was sonicated for 15 minutes at 150watts (8 seconds on and 2 seconds off).
Characterization Particle The morphology of the prepared sample was observed using the Scanning electron microscopy (SEM)
after each size reduction method.
Particle size
Diameter size was measured with a dynamic light scattering analyzer(DLS).
Entrapment efficiency and drug loading capacity
10ml of suspension was centrifuged via ultracentrifuge at 30,000rpm (100,000 × g) at 25°C for 15 minutes. The supernatant containing the free drug was separated from the pellet. Then its absorption at 276nm was measured with a spectrophotometer. Furthermore, the desired parameters were obtained using the following equations:
"EE%" "=" "(the initial amount of doxycycline - the amount of doxycycline in the supernatant)" /"the initial amount of doxycycline" "×100"
"LC% = " "(weight of initial doxycycline-weight of free doxycycline)" /"weight of nano-niosomes" "×100"
Drug release
The synthesized formulation and free-drug (with the equivalent drug) were transferred to a dialysis bag (12,400Mv cut-off) in a beaker with a content of 20 ml PBS (at 37°C and a vortex of 100rpm). 1ml sample was taken from the inside beaker at 0.25, 0.5, 1, 2, 4, 8, 16, and 32hours. The absorbance was measured at 276nm. Finally, drug release data were analyzed using Zero-order, Higuchi, and Korsmeyer-Peppas kinetic models.
Results: SEM:The bathing method had almost no effect on reducing the sample size. The inefficiency of the extrusion method was also observed. Span60 is solid at room temperature, and extrusion must be performed at temperatures above Tc of surfactant because it has a low velocity at temperatures below Tc due to the higher gel viscosity of the membrane and reduced ductility. The extrusion method also changed the morphology of the niosomes, which may be due to the low percentage of cholesterol in the sample structure, which loses its flexibility when exposed to high force. Therefore, size reduction with the probe sonicator is the best way to reduce sample size.
Particle size: The DLS results showed an average particle size of 213.76±12.75nm.
The entrapment and loading capacity of the drug: The obtained values were 39.7±1.8 and 13.4±0.6, respectively.
Drug release: Controlled and slow drug release from the prepared formulation compared to the free-drug was observed after 32 hours. The most consistent release data were with the Korsmeyer-Pappas model ("R" ^"2" " ≥ 97%" ).
Conclusion: The sample synthesized by the thin-film hydration method and probe sonication had a suitable size for dermal delivery, and the drug entrapment efficiency was appropriate. In addition, controlled release of the drug prevents skin side effects compared to the free drug and reduces the need for re-dosing. Thus, in general, the synthesized sample can be used in dermal delivery and skin infections